JP-A 4-46115 and JP-A 4-46116 (EP-A-461630) disclose a process for producing microspheres of water-soluble drugs by oil-in-water (O/W) type in-liquid drying process wherein the solvent of the oil phase is composed of at least one water-insoluble solvent and at least one water-miscible solvent as well as preparation of microspheres wherein an aliphatic acid salt is added to the oil phase. Further, the abstract of the 112th Annual Meeting of the Pharmaceutical Society of Japan (IV, p. 86) discloses microspheres obtained from an O/W type emulsion of a water-soluble drug by dissolving a high molecular polymer in the first solvent to disperse the drug, (2) adding the second solvent for homogeneous dissolution, and then (3) subjecting the resulting solution to O/W type in-liquid drying.
Journal Microencapsulation, 1988, Vol. 5, No. 2, p. 147-157 describes preparation of microcapsules of water-soluble drugs from an oil-in-oil (O/O) type emulsion wherein the internal phase is composed of a water-miscible solvent and the external phase contains silicone oil, vegetable oil and the like.
However, in preparation of microspheres by O/W type in-liquid drying process, the water-soluble drug take up into microspheres is insufficient and unsatisfactory. Further, O/O type in-liquid drying process has disadvantages. For example, it requires a large amount of solvent and heating at high temperature upon drying.